cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]
cc1: warning: include location "/usr/include/libpng16" is unsafe for cross-compilation [-Wpoison-system-directories]

From my experience this weekend with mpfr and coreutils, these warnings hint that the build is using my system libraries and includes instead of the ones found in the cross-compile environment. A quick glance at the config.log file reveals just that:

As best as I can tell there is not configure parameter available for changing this specific library location... it may be possible to provide configure a cached result of the location of the library, but then that implies that the library exists, which may not always be true (well, portage makes sure that the dependencies are installed, but sometimes things slip through the cracks). I'll keep working on this as I have time this upcoming week. Thoughts?

The correct way for a configure script to find a package is to ask pkg-config for the CFLAGS/LDFLAGS required to use it. In turn, a properly prepared cross-compile environment should cause pkg-config to return the flags for the cross-system directories instead of the native directories. Could you provide the config.log context (~100 lines) around where it reports result: -L/usr/lib64 -lpng16?